tbuckley/cabot-search huggingface dataset:
Efficacy and safety of mFOLFOX6 with apatinib as postoperative adjuvant chemotherapy in stage IIIB or IIIC colorectal cancer.
Authors: Xiaodong Gu, Minwei Zhou, Zihao Wang, Zhenyang Li, Yi Yang, Yiwen Zang, Yiming Zhou, Jianbin Xiang, Zongyou Chen
Journal: Journal of Clinical Oncology (2023)

3613 Background: Antiangiogenic therapy has shown benefit in metastatic colorectal cancer. However, the role of apatinib in adjuvant treatment of stage IIIB and IIIC colorectal cancer remains unclear. Methods: Patients received modified FOLFOX6 once every 2 weeks for a 6-month period (control group) or modified FOLFOX6 for 6 months plus apatinib (500mg) once a day for a 12-month period (experimental group). Progression free survival (PFS), overal survival (OS) and treatment-related adverse events were evaluated in two groups. Results: 63 patients have been enrolled in this study. This trial reported a 3-year PFS of 74.2% for modified FOLFOX6 plus apatinib vs. 61.5% for modified FOLFOX6 ( P&lt; 0.05). 5-year OS was significantly improved in the experimental group compared with the control group (86.3% vs. 72.5%; P&lt; 0.05). The most common grade 3 adverse events were hypertension and hand–foot syndrome. No treatment-related grade 4 adverse events or treatment-related deaths were observed. Conclusions: Apatinib can prolong PFS and OS when added to adjuvant chemotherapy in resected stage IIIB and IIIC colorectal cancer. The toxicities associated with apatinib were generally acceptable. Clinical trial information: NCT03365765 .
Socioeconomic and demographic disparities in rectal cancer treatment.
Authors: Vernon Wu, Molly Kobritz, Diana Kantarovich, Baho Sidiqi, Leila Tchelebi, Richard L Whelan, Daniel King
Journal: Journal of Clinical Oncology (2023)

e15512 Background: Early treatment (tx) improves survival in rectal cancer (ca). We explored whether socioeconomic and demographic attributes are associated with time to tx initiation for rectal ca patients (pts) in New York's largest and most diverse healthcare system. Methods: 283 rectal ca pts were identified from three multidisciplinary tumor boards from 2019-2022. Time to tx was calculated as time from biopsy to first tx (surgery, chemotherapy, or radiation). Social work assistance was defined as an intervention by a social worker for home care, housing, or transportation assistance. Reasons for tx delay were assessed from physician and social work notes. Results: Median time to tx for all pts was 41 days. Time to tx was longer for Black/African American (BAA) (56.5 days; p &lt; 0.001) and Medicare only (46.5 days; p = 0.005) pts. No differences were seen in time to tx for all pts when stratified by first tx modality (surgery, chemotherapy, or radiation). In a univariable linear regression, BAA pts (vs Asian or White; p &lt; 0.001), Medicare only pts (vs Medicaid, Medicare with Supplemental, or Commercial Insurance; p = 0.001), and pts requesting social work assistance (p = 0.001) predicted longer time to tx. Employed pts (vs unemployed or retired; p = 0.034) predicted shorter time to tx. In a multivariable model, BAA (p = 0.013), Medicare (p = 0.022), and social work assistance (p = 0.029) predicted longer time to tx. The most common reasons identified for tx delay in BAA and Medicare pts were hospitalization during diagnosis (9%), evaluation of metastatic disease (9%), and tx hesitancy (7%). The odds ratio of being hospitalized during initial workup was 2.8 times higher for BAA than Asian or White pts (p = 0.007). Conclusions: Analysis of time to tx in rectal ca showed a notable delay for BAA pts, Medicare only pts, and pts requesting social work assistance. These findings may empower further studies to assess which factors are causal and to implement interventions that promote equity in timely tx for rectal ca pts. Reasons for tx delay were also not well documented and should be further elucidated. [Table: see text]
A randomized trial of olaparib, durvalumab, and cancer vaccine, UV1, as maintenance therapy in patients with BRCAwt with recurrent ovarian cancer: ENGOT-OV56/NSGO-CTU-DOVACC trial.
Authors: Mansoor Raza Mirza, Klaus Pietzner, Els Van Nieuwenhuysen, Christian Marth, Ingrid Boere, Kristina Lindemann, Josefin Fernebro, Sakari Hietanen, Birute Brasiuniene, Kirsten Pors, Signe Gybel Frederiksen, Ulrikke Ji Mee Willerslev, Elena Ioana Braicu, Kristine Madsen, Flora Zagouri
Journal: Journal of Clinical Oncology (2023)

TPS5615 Background: Most ovarian cancers (OC) are diagnosed at an advanced stage and despite initial therapy, the disease will often relapse and require further treatment Thus, there is a need for novel therapeutic options. PARP inhibitors lead to increasing tumour neoantigen, and modulation of the tumour microenvironment, which may facilitate a more profound antitumour immune response. UV1 is a therapeutic cancer vaccine directed against telomerase. Since telomerase is an essential enzyme and universally expressed by most tumor cells, it represents a unique cancer antigen as a basis for immunotherapy (IO). The rationale for integrating immunotherapy as maintenance therapy following chemotherapy is based on preclinical studies which have shown that chemotherapy induces immunogenic cell death leading to increased recognition of the tumor by the immune system. The proposed study is evaluating the use of the therapeutic cancer vaccine UV1 in combination with olaparib and the PD-L1 inhibitor, durvalumab as maintenance therapy after response to platinum-based chemotherapy. Methods: The primary objective is to demonstrate efficacy of UV1-olaparib-durvalumab combination maintenance therapy against olaparib in maintenance after platinum combination therapy for BRCAwt patients with relapsed ovarian cancer. Key eligibility criteria include: histologically confirmed, platinim sensitive recurrent OC in response to last platinum-containing chemotherapy, BRCAwt. Patients may be previously treated with PARPi, however prior IO is not permitted. Patients are stratified by HRD status and previous use of PARPi. 184 patients are randomized to three arms (1:1:2): arm A: olaparib single agent, arm B: olaparib-durvalumab and arm C: olaparib, durvalumab-UV1. Duration of therapy: olaparib until progression of disease; durvalumab for 24 months; intradermal UV1, 8 doses within 5 months. Intradermal sargramostim is used as vaccine adjuvant. Primary endpoint is progression-free survival (PFS) of arm C versus arm A. Key secondary endpoints include PFS arm B versus C, patient reported outcomes, and overall survival. This NSGO-CTU sponsored trial is enrolling patients in 11 countries. The following cooperative groups are participating: NSGO-CTU (DK, FIN, NOR, SWE, LTU), BGOG (BE), HeGOG (GRC, CYP), NOGGO (DE), AGO-A (AUT) &amp; DGOG (NL). Clinical trial information: NCT04742075 .
Phase II study of border zone stereotactic radiosurgery with bevacizumab in patients with recurrent or progressive glioblastoma multiforme.
Authors: Megan Mantica, Jan Drappatz, L. Dade Lunsford, Frank S. Lieberman, Ajay Niranjan
Journal: Journal of Clinical Oncology (2023)

e14020 Background: This phase II trial was performed to assess the efficacy of Border Zone Stereotactic Radiosurgery (BZ-SRS) with bevacizumab by overall survival (OS) in patients with recurrent or progressive glioblastoma (GBM) following conventional upfront management. Methods: Patients with histologically confirmed GBM with recurrent disease, received prior first-line treatment with surgery/biopsy, fractionated radiotherapy and chemotherapy, ≥ 2 months since completion of radiotherapy and eligible for SRS were enrolled. Bevacizumab 10mg/kg was given one day before, day 14 and then every 14 days until disease progression. 1 to 14 days before BZ-SRS procedure, patients underwent standard brain MRI /MRS. MRS with measurement of choline-to-N-acetyl aspartate index (CNI) area ≥ 3 was targeted for SRS using standard MRI targeting. Results: From 2015-2017, sixteen patients were enrolled. The median age was 62 (range, 48-74Y). 3 of 16 (0.188) participants experienced grade 2 unacceptable toxicity. The median OS was 11.73 months. No survival difference is seen compared with the University of Pittsburgh historical controls. PFS-6 and OS-6 were 31.2% (p=0.00294) and 81.2%(p= 0.058), respectively. Of 13 evaluable for best response: 1 complete response (p=0.077), 4 partial responses (p=0.308), 7 stable disease (p=0.538), and 1 progressed disease (p=0.077). 11 of 16 participants had MRS scans with an estimated probability that MRS changes a treatment plan of 0 (0,0.285). Conclusions: BZ-SRS with bevacizumab was feasible and well tolerated. There is no significant survival benefit using BZ-SRS with bevacizumab compared to historical controls. Secondary analysis revealed a trend toward improved PFS-6, but not OS-6. MRS scans did not result in any changes in SRS treatment plans. Clinical trial information: NCT02120287 .
Characteristics of local extension based on tumor distribution in nasopharyngeal carcinoma and proposed clinical target volume delineation.
Authors: Zheng Wu, fei-Fei Lin, Lin Zhang, Qian He, Feiping Li, Hui Wang, Yaqian Han, wen-Jing Yin, Bin Qi
Journal: Journal of Clinical Oncology (2023)

e18068 Background: to summarize the characteristics of local extension of the eccentric and central nasopharyngeal carcinoma (NPC) by magnetic resonance imaging (MRI) and to improve clinical target volume (CTV) delineation. Methods: MRIs of 870 newly diagnosed NPC patients were reviewed. According to the tumor distribution feature, the NPCs were divided into eccentric and central lesions. Results: All local invasions presented as continuous invasion from gross lesions and structures adjacent to the nasopharynx are more likely to be invaded. There were 240 (27.6%) and 630 (72.4%) cases with central and eccentric lesions, respectively. The spread of eccentric lesions centered on the ipsilateral Rosenmüller’s fossa; and most anatomic sites had significantly higher invasion rates in ipsilateral side than the contralateral side ( P &lt; 0.05); however, they were at low risk of concurrent bilateral tumor invasion ( &lt; 10%) except the prevertebral muscle (15.4%) and nasal cavity (13.8%). The extension of central NPCs centered on the nasopharyngeal superior-posterior wall and was more common in superior-posterior direction; furthermore, the bilateral tumor invasion into the anatomical sites was common. Conclusions: Local invasion of NPC was characterized by continuous invasion from proximal to distal sites. The eccentric and central lesions showed different invasion features. Individual CTV delineation should be based on the distribution characteristics of tumors. The eccentric lesion had very low probability of invasion into the contralateral tissue, thus routine prophylactic radiation of contralateral parapharyngeal space and skull base foramina may not be necessary.
Clinical and radiological criteria for candidate patients with small bowel neuroendocrine neoplasms (SB-NEN) for minimally invasive surgery: A single-centre experience.
Authors: Lorenzo Guidi, Guglielmo Conti, Alessandro Michele Bonomi, Francesca Spada, Lorenzo Gervaso, Chiara Alessandra Cella, Emilio Bertani, Fabio Zugni, Lavinia Benini, Michele Borghesani, Laura Algeri, Giuseppe Curigliano, Luigi Funicelli, Uberto Fumagalli Romario, Nicola Fazio
Journal: Journal of Clinical Oncology (2023)

e16246 Background: Although open resection represents the standard of care of localized small bowel neuroendocrine neoplasms (SB-NEN), minimally invasive surgery (MIS) has proven to be a viable alternative in patients with low disease burden. This study aims to assess the reliability of preoperative clinical and radiological criteria used at European Institute of Oncology (IEO) to candidate patients with SI-NEN to MIS. Methods: Patients diagnosed with SB-NEN and eligible for MIS at IEO were retrospectively evaluated between 2013 and 2022. Preoperative physical examination, CT enterography (CTE) and Ga68-DOTATOC-PET-CT were used for clinical staging. At IEO NEN multidisciplinary tumor board, the following eligibility criteria were adopted to candidate patients to MIS (curative or palliative): number and localization of primary tumor, grade of superior mesentery artery and vein encasement by lymph-node metastases of 0-2 according IEO criteria (based on Lardiere-Degalte classification). Information on morphology and carcinoid syndrome were collected. The primary endpoint was laparotomy conversion rate. Results: Twelve patients were selected. Patients’ characteristics are available. Median age at surgery was 55 years (range: 33–73). Among these patients, based on pathological findings, 8 (67%) had confirmed nodal involvement, 3 (25%) metastatic disease and 4 (33%) multifocal primary tumor. Vascular involvement (based on IEO criteria) was found in 9 patients (75%). Of note, only 3 (25%) patients had a functioning tumor as a preoperative finding and all tumors resulted well-differentiated. Among 12 patients which underwent laparoscopic surgery, none has been converted to laparotomy surgery. After a median follow-up of 25.3 months (range: 2.5-71.3), the 1-year disease free survival for non-metastatic patients was of 100%. Conclusions: the assessment of tumor burden with 68 Ga-PET-CT and CTE according to IEO criteria could be a reliable method to candidate patients affected by SB-NEN to MIS, according to a multidisciplinary approach.[Table: see text]
Preclinical testing of FOLR1-CAR T cells against osteosarcoma (OS).
Authors: Michelle Choe, Danielle Kirkey, Rhonda E Ries, Tiffany Hylkema, Sarah J Menashe, Lara E. Davis, Michael J Wagner, Lee D. Cranmer, Sanjay Malhotra, Richard Greg Gorlick, Soheil Meshinchi, Elizabeth Trice Loggers
Journal: Journal of Clinical Oncology (2023)

2555 Background: Survival rates for OS are poor. Prior literature suggests folate receptor-a (FOLR1) overexpression in OS, making it a target for CAR T development. Methods: OS transcriptome data from TCGA, PCGP and NCI PIVOT programs were interrogated for FOLR1 gene expression. A 2 nd generation FOLR1-CAR T cell was created by fusing the ScFv from farletuzumab (anti-FOLR1 monoclonal antibody) with a 4-1BB costimulatory and CD3z cytotoxicity domain. Non-transduced (NT) T cells served as controls. In vitro functional analysis was performed against U2OS cell line using flow cytometry (FC) and Incucyte. U2OS xenograft in NSG mice was generated via intra-femoral inoculation for local tumor and via tail vein (TV) tumor injection for pulmonary disease. Tumor engraftment was confirmed by in vivo imaging system (IVIS). Disease progression was monitored by IVIS and CT imaging. 5 million T cells were administered via TV. Circulating human T cells (HTC) collected from retro-orbital peripheral blood (PB) were detected via FC. Results: FOLR1 transcript was expressed in &gt;75% of OS in TCGA, PCGP and PIVOT. In vitro evaluation of FOLR1-CAR T demonstrated robust antitumor activity (E:T ratio 1:1) with cytotoxicity of 76.5% and 95.5% at 6 and 24 hrs. Disease progression was observed in NT T cell treated mice, with an average fold increase in IVIS radiance of 35.1 in local (n=2) and 142.8 in pulmonary disease (n=3) over 11 weeks (wks) versus complete resolution of local (n=2) and pulmonary disease (n=3) in FOLR1-CAR T treated mice (see table). NT T treated mice with local disease demonstrated significant bone destruction; no local tumors were found in FOLR1-CAR T treated mice. HTC (CD45+/CD3+) expansion was detected in PB one wk post-treatment (PT); in mice with metastasis 0.190% and 0.136% of live circulating cells were human T cells in FOLR1-CAR T and NT T treated mice, respectively. Improved overall survival was observed in FOLR1-CAR T treated mice (&gt;100 vs 87.5 days). Conclusions: FOLR1-CAR T cells appear to have in vivo activity against U2OS cell line and support further testing of safety and feasibility in an early phase clinical trial for relapsed/refractory OS. [Table: see text]
Transarterial chemoembolization combined with lenvatinib and camrelizumab for unresectable hepatocellular carcinoma: A prospective, single-arm, multicenter study.
Authors: Zhibo Zhang, Maolin Yan, Yufeng Chen, Xukun Wu, Lanfang Yang, Zhengyu Yin, Hao Lu, Yongyi Zeng, Hui Zhang, Jingyao Huang, Jiafei Chen, Liang Wang, Zhongwu Chen
Journal: Journal of Clinical Oncology (2023)

4072 Background: Conversion therapy for unresectable hepatocellular carcinoma (uHCC) has attracted increasing interest in recent years. In 2020 ASCO annual meeting, one abstract reported that the combination therapy of tyrosine kinase inhibitor and anti-PD-1 antibody could be a promising conversion therapy for patients with initially uHCC. This study aims to evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with lenvatinib and camrelizumab (TACE+LEN+CAM) as a conversion therapy for uHCC. Methods: This single-arm, prospective, multicenter study was conducted on patients diagnosed with HCC (with an Eastern Cooperative Oncology Group performance score (ECOG PS) of 0-1 and Child-Pugh class A) who were ineligible for surgery. Enrolled patients received camrelizumab (200 mg every 3 weeks) and lenvatinib (bodyweight ≥ 60 kg: 12 mg/day; &lt; 60 kg: 8 mg/day) after TACE treatment. Surgery was performed after treatment response was assessed to meet the criteria of resection. Patients who did not meet the criteria for surgery continued to receive triple treatment until disease progression or intolerable toxicity. Primary endpoints were objective response rate (ORR)and safety. Secondary endpoints included percentage of patients amendable to surgery, the rate of radical (R0) resection, disease control rate (DCR). This study is registered with Chinese Clinical Trial Registry (ChiCTR2100050410). Results: Between Oct 25, 2021, and Jul 20, 2022, 55 patients were enrolled and received triple therapy (TACE+LEN+CAM). Of these, 37 (67.3%) patients had portal vein tumor thrombosis. Mean tumor diameter for all patients was 112 ± 83 mm. 52 (94.6%) patients with≤2 target lesions, and 3 (5.4%) patients with &gt; 2 target lesions. As of data cutoff on Dec 20, 2022, the median follow-up was 6.7 months (IQR 5.0-9.89). According to modified RECIST criteria, tumor response in patients included complete response to treatment in 9 patients (18.0%), partial response in 27 (54.0%), stable disease in 6 (12.0%), and progressive disease in 7 (14.0%). The ORR was 72.0%, and the DCR was 84.0%. 26 patients underwent surgery after successful conversion therapy. The MPR and pCR rates in the surgery population were 69.2% and 23.1%, respectively. The conversion rate was 55.3% and the R0 resection rate was 100%. 23 (41.8%) of 55 patients had treatment-related adverse event (TRAEs) that were grade 3-5. No grade 3-5 TRAEs occurred after surgery. Conclusions: The triple therapy (TACE+LEN+CAM) significantly improved ORR and the surgical conversion rate of uHCC patients with a manageable safety. Future large-scale randomised trials are warranted. Clinical trial information: ChiCTR2100050410 .
The impact of next generation sequencing on the management of urothelial cell carcinoma.
Authors: Hussein Abu-Hashish, Rasheda Browne, Xinhua Zhu
Journal: Journal of Clinical Oncology (2023)

e16576 Background: The urothelial carcinoma is commonly seen in urethra, bladder, ureter and renal pelvis. Targetable mutations included PD-L1, FGFR, PIK3CA, BRCA2, FBXW7, and Tumor mutation burden (TMB) greater than 10 Muts/Mb. Next genome sequencing is widely used to guide treatment of oncology patients; however, the efficacy of this practice is still not clear. Methods: Patients used in this study are from the Northwell Health Zuckerberg Cancer Center. This is a retrospective cohort study of patients with advanced urothelial carcinoma, who underwent next genome sequencing and received treatment based on targetable mutations. The primary objective for this study is to measure the response rate for patients with actionable gene aberrations on targetable treatment. Results: The RECIST 1.1 guidelines were used when identifying measurable lesions. Measurable lesions were identified as lymph nodes with a short axis ≥ 15 mm, or soft tissue lesions with a long axis ≥ 10 mm. Our sample size included 48 patients with urothelial carcinoma, these include bladder, ureter and renal pelvis cancers. Of these 48 patients, 21 received targetable treatment (16 males, 5 females), from those 21 only 20 had imaging before and after treatment. Most common mutations were TMB, PD-L1 and FGFR. 4 patients out of 20 had an overall response rate (20%), 3 had partial response (PR) and 1 had complete response (CR) to their respective targeted treatment. 11 patients had stable disease (SD). Thus disease control rate (DCR) was 15 out of 20 patients (75%) (when including PR, CR and SD out of 20 patients) had no progression of disease. Finally, 5 of the 20 patients had an overall progression of disease (PD). Conclusions: The results of our study indicate that next genome sequencing led to good treatment outcomes for patients previously heavily treated with advanced urothelial malignancy.
The five periampullary cancers: Not just different siblings but different families—An international multicenter cohort study.
Authors: Bas Uijterwijk, Santiago Cabus, Vasileios K. Mavroeidis, Patrick Pessaux, Dimitris Korkolis, Adam C. Berger, Bergthor Björnsson, Miguel Suárez, Miljama Vladimirov, Jorg Kleeff, Ugo Boggi, Zahir Soonawalla, Alberto Zaniboni, Mario Serradilla, Michele Mazzola, Poya Ghorbani, Ulrich Wellner, Marc G. Besselink, Mohammed Abu Hilal
Journal: Journal of Clinical Oncology (2023)

4167 Background: Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC) and ampullary adenocarcinoma (AAC). Based on histopathology, the AAC is currently subdivided in the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype. Despite close anatomical resemblance, it is unclear how the ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior. Methods: This is an international multicenter cohort study, including patients after curative intent resection for periampullary cancer retrieved from 45 centers (from Europe, USA, Asia and Canada) between 2010 and 2021. Pre-operative CA19-9, differences in pathology and postoperative pancreatic fistula (POPF, grade B/C), 8-year overall survival (OS) and disease-free interval (DFI) were compared between DAC, AmpIT, AmpPB, dCCA and PDAC. Results: Overall, 3809 patients were included of which 348 DAC, 774 AmpIT, 848 AmpPB, 1036 dCCA and 803 PDAC. The best 8-years overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, p&lt;0.001), dCCA (26.4%, p=0.020) and last, PDAC (12.9%, P&lt;0.001). The best 8-years DFI was measured for AmpIT (62.7%) and the worst for both dCCA and PDAC (24.9% and 21.8%). This pattern correlated with the height of the pre-operative CA19-9 but not with the pathology, in which the largest and most progressed tumors were found in DAC. The incidence of POPF was lower in the pancreas-related tumor types (AmpPB 18.5%, PDAC 8.3%) compared to the non-pancreas related types (DAC 27.3%, AmpIT 25.5%, dCCA 27.6%). Conclusions: Despite the close anatomic relation of the five periampullary cancers, this study shows that there are prognostic and clinically relevant differences in terms of preoperative blood markers, pathology, complications, long-term survival, and recurrence. More characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for “periampullary cancers”, this study emphasizes the need for individual evaluation of each histopathological periampullary subtype with the ampullary subtypes as individual entities in future studies.